The taste system plays a major role in informing organisms on the choice of diet and, consequently, understanding the functioning of this system may lead to the development of treatments for health conditions that are subject to dietary influences including obesity, diabetes, and heart disease. Five basic taste qualities - sweet, salty, bitter, umami, and sour - are encoded by peripheral cells within taste buds of the tongue and encoded into distinct qualities. For many of these, the receptors have been identified and shown to be expressed in subsets of cells within the taste bud. The receptor for sour is currently unknown, but sour cells are faithfully marked by expression of the Transient Receptor Potential (TRP) ion channel Pkd2l1. Intriguingly, accumulating evidence suggests that sour cells have the capacity to transmit or modulate sensations other than sour. For example, the aversive response to high salt is mediated, in part, by cells that express Pkd2l1. In addition, activation o G protein-coupled receptors (GPCRs) and ion channels that do not function as sour receptors can cause release of neurotransmitters from sour cells. Detailed knowledge of the molecular constituents of sour cells will help establish signaling pathways involved in sour cell activity. I preliminary work, the transcriptome of Pkd2l1-expressing sour cells was profiled to identify putative receptors and signaling intermediaries involved in sour and potentially other taste qualities. Results showed the unique expression of two previously unidentified TRP channels in sour taste cells. TRP channels are expressed in numerous sensory cell types and can function as receptors for extracellular stimuli and as sensors of the intracellular environment. The proposed work will test the following HYPOTHESIS: Two previously unidentified TRP ion channels are downstream effectors of intracellular signaling cascades that stimulate sour cell activity. Using computational approaches, molecular and cellular methods, and electrophysiology, this proposal presents experiments aimed at substantiating the roles of these two TRP channels in taste signaling. By furthering our understanding of the molecular physiology of the taste system, this work may lead to the development of strategies to combat human diseases that result from poor dietary choices.